Subscribe to RSS
![](/products/assets/desktop/img/oa-logo.png)
DOI: 10.1055/s-0041-1741443
Analysis of Prediagnostic Circulating Levels of Gonadotropins and Androgens with Risk of Epithelial Ovarian Cancer
Funding We did not receive any funding for this research work.![](https://www.thieme-connect.de/media/10.1055-s-00044881/202201/lookinside/thumbnails/10-1055-s-0041-1741443_2150685-1.jpg)
Abstract
Background Prevailing experimental and epidemiological evidence supports the role of circulating endogenous sex steroid hormones in the pathogenesis of ovarian carcinogenesis by dysregulation of cell differentiation, proliferation, and apoptosis but is scarce and inconclusive.
Objectives This article evaluates the role of circulating levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and androgens (testosterone, dehydroepiandrosterone-sulfate [DHEA-S]) for the risk of epithelial ovarian cancer in a case–control approach using samples collected in advance of clinical diagnosis.
Materials and Methods A total of 100 epithelial ovarian cancer (EOC) patients and 100 healthy female controls were consequently enrolled in this hospital-based case–control study. Serum FSH, LH, testosterone, and DHEA-S were measured based on the principle of electrochemiluminescence immunoassay. Suitable descriptive statistics were used for different variables.
Results Median values of FSH (58.9 vs. 45.5 IU/L, p = 0.02) and DHEA-S (163.43 vs. 142.2 ug/dL, p = 0.03) were significantly high in EOC patients compared with controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH and DHEA-S concentrations, and the results revealed that the highest third tertile of FSH (> 72.6 IU/L; OR = 3.0, confidence interval [CI] = 1.24–7.29, p trend = 0.04) and DHEA-S (> 194.2 ug/dL; OR = 3.8, CI = 1.26–11.61, p trend = 0.03) were significantly associated with increased risk of ovarian cancer in postmenopausal and premenopausal women, respectively. The statistically significant trend observed for FSH in postmenopausal women, remained only for the subgroup with menopause duration greater than 10 years (OR = 5.9, CI = 1.33–26.66, p trend = 0.04). FSH and DHEA-S concentrations and ovarian cancer risk were internally consistent with groups defined by oral contraceptive pill use, hormone replacement therapy, and smoking. However, no evidence was found for the association between serum LH and testosterone level with the occurrence of ovarian tumorigenesis.
Conclusion Prediagnostic circulating concentration of FSH and DHEA-S unveiled a significant positive association with augmented risk of EOC, thus might serve as a predictive marker for the susceptibility to ovarian carcinogenesis and should be added in the screening profile of EOC for early recognition and scheduling necessary interventions/management strategies.
Publication History
Article published online:
18 January 2022
© 2022. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69 (01) 7-34
- 2 Takiar R. Status of ovarian cancer in India. EC Gynaecol 2019; 8 (05) 358-364
- 3 Maheshwari A, Kumar N, Mahantshetty U. Gynecological cancers: a summary of published Indian data. South Asian J Cancer 2016; 5 (03) 112-120
- 4 Lynch HT, Casey MJ, Snyder CL. et al. Hereditary ovarian carcinoma: heterogeneity, molecular genetics, pathology, and management. Mol Oncol 2009; 3 (02) 97-137
- 5 Zhu H, Zhu X, Zheng L, Hu X, Sun L, Zhu X. The role of the androgen receptor in ovarian cancer carcinogenesis and its clinical implications. Oncotarget 2017; 8 (17) 29395-29405
- 6 Mizushima T, Miyamoto H. The role of androgen receptor signaling in ovarian cancer. Cells 2019; 8 (02) 176
- 7 Li S, Jiang K, Li J. et al. Estrogen enhances the proliferation and migration of ovarian cancer cells by activating transient receptor potential channel C3. J Ovarian Res 2020; 13 (01) 20
- 8 Modugno F, Laskey R, Smith AL, Andersen CL, Haluska P, Oesterreich S. Hormone response in ovarian cancer: time to reconsider as a clinical target?. Endocr Relat Cancer 2012; 19 (06) R255-R279
- 9 Rinaldi S, Dossus L, Lukanova A. et al. Endogenous androgens and risk of epithelial ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Epidemiol Biomarkers Prev 2007; 16 (01) 23-29
- 10 Lonard DM, O'Malley BW. Nuclear receptor coregulators: modulators of pathology and therapeutic targets. Nat Rev Endocrinol 2012; 8 (10) 598-604
- 11 Peres LC, Moorman PG, Alberg AJ. et al. Lifetime number of ovulatory cycles and epithelial ovarian cancer risk in African American women. Cancer Causes Control 2017; 28 (05) 405-414
- 12 Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health 2019; 11 (11) 287-299
- 13 Daniilidis A, Dinas K. Long term health consequences of polycystic ovarian syndrome: a review analysis. Hippokratia 2009; 13 (02) 90-92
- 14 Ose J, Poole EM, Schock H. et al. Androgens are differentially associated with ovarian cancer subtypes in the ovarian cancer cohort consortium. Cancer Res 2017; 77 (14) 3951-3960
- 15 Olsen CM, Green AC, Nagle CM. et al; Australian Cancer Study Group (Ovarian Cancer) and the Australian Ovarian Cancer Study Group. Epithelial ovarian cancer: testing the ‘androgens hypothesis’. Endocr Relat Cancer 2008; 15 (04) 1061-1068
- 16 Li AJ, Karlan BY. Androgens and epithelial ovarian cancer: what's the connection?. Cancer Biol Ther 2008; 7 (11) 1712-1716
- 17 Gründker C, Emons G. Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer. Cells 2021; 10 (02) 437
- 18 Zheng H, Kavanagh JJ, Hu W, Liao Q, Fu S. Hormonal therapy in ovarian cancer. Int J Gynecol Cancer 2007; 17 (02) 325-338
- 19 Williams C, Simera I, Bryant A. Tamoxifen for relapse of ovarian cancer. Cochrane Database Syst Rev 2010; 2010 (03) CD001034
- 20 Desai A, Xu J, Aysola K. et al. Epithelial ovarian cancer: an overview. World J Transl Med 2014; 3 (01) 1-8
- 21 Meeta DL, Digumarti L, Agarwal N, Vaze N, Shah R, Malik S. Clinical practice guidelines on menopause: an executive summary and recommendations. J Midlife Health 2013; 4 (02) 77-106
- 22 Rzepka-Górska I, Chudecka-Głaz A, Kosmowska B. FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary. Endocr Relat Cancer 2004; 11 (02) 315-321
- 23 Choi JH, Wong AS, Huang HF, Leung PC. Gonadotropins and ovarian cancer. Endocr Rev 2007; 28 (04) 440-461
- 24 Vanderhyden BC. Loss of ovarian function and the risk of ovarian cancer. Cell Tissue Res 2005; 322 (01) 117-124
- 25 Lukanova A, Lundin E, Akhmedkhanov A. et al. Circulating levels of sex steroid hormones and risk of ovarian cancer. Int J Cancer 2003; 104 (05) 636-642
- 26 Arslan AA, Zeleniuch-Jacquotte A, Lundin E. et al. Serum follicle-stimulating hormone and risk of epithelial ovarian cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2003; 12 (12) 1531-1535
- 27 Ose J, Poole EM, Schock H. et al; Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium. Androgens are differentially associated with ovarian cancer subtypes in the ovarian cancer cohort consortium. Cancer Res 2017; 77 (14) 3951-3960
- 28 Keri RA, Lozada KL, Abdul-Karim FW, Nadeau JH, Nilson JH. Luteinizing hormone induction of ovarian tumors: oligogenic differences between mouse strains dictates tumor disposition. Proc Natl Acad Sci U S A 2000; 97 (01) 383-387
- 29 Halperin R, Pansky M, Vaknin Z, Zehavi S, Bukovsky I, Schneider D. Sackler Faculty of Medicine, Tel Aviv University, Israel. Luteinizing hormone in peritoneal and ovarian cyst fluids: a predictor of ovarian carcinoma. Eur J Obstet Gynecol Reprod Biol 2003; 110 (02) 207-210
- 30 Tworoger SS, Lee IM, Buring JE, Hankinson SE. Plasma androgen concentrations and risk of incident ovarian cancer. Am J Epidemiol 2008; 167 (02) 211-218
- 31 McSorley MA, Alberg AJ, Allen DS. et al. Prediagnostic circulating follicle stimulating hormone concentrations and ovarian cancer risk. Int J Cancer 2009; 125 (03) 674-679
- 32 Chen FC, Oskay-Ozcelik G, Bühling KJ. et al. Prognostic value of serum and ascites levels of estradiol, FSH, LH and prolactin in ovarian cancer. Anticancer Res 2009; 29 (05) 1575-1578
- 33 Irvin SR, Weiderpass E, Stanczyk FZ. et al. Association of anti-Mullerian hormone, follicle-stimulating hormone, and inhibin B with risk of ovarian cancer in the Janus Serum Bank. Cancer Epidemiol Biomarkers Prev 2020; 29 (03) 636-642
- 34 Chudecka-Głaz A, Rzepka-Górska I, Kosmowska B. Gonadotropin (LH, FSH) levels in serum and cyst fluid in epithelial tumors of the ovary. Arch Gynecol Obstet 2004; 270 (03) 151-156
- 35 Helzlsouer KJ, Alberg AJ, Gordon GB. et al. Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA 1995; 274 (24) 1926-1930
- 36 Akhmedkhanov A, Toniolo P, Zeleniuch-Jacquotte A, Pettersson KS, Huhtaniemi IT. Luteinizing hormone, its beta-subunit variant, and epithelial ovarian cancer: the gonadotropin hypothesis revisited. Am J Epidemiol 2001; 154 (01) 43-49
- 37 Ushiroyama T, Sakai M, Higashiyama T, Ikeda A, Ueki M. Estrogen replacement therapy in postmenopausal women: a study of the efficacy of estriol and changes in plasma gonadotropin levels. Gynecol Endocrinol 2001; 15 (01) 74-80
- 38 Lee AW, Ness RB, Roman LD. et al; Ovarian Cancer Association Consortium. Association between menopausal estrogen-only therapy and ovarian carcinoma risk. Obstet Gynecol 2016; 127 (05) 828-836
- 39 Ciucci A, Zannoni GF, Buttarelli M. et al. Multiple direct and indirect mechanisms drive estrogen-induced tumor growth in high grade serous ovarian cancers. Oncotarget 2016; 7 (07) 8155-8171
- 40 Sood AK, Bhatty R, Kamat AA. et al. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res 2006; 12 (02) 369-375